Tyrosine Metabolism

Tyrosine is produced in cells by hydroxylating (via phenylalanine hydroxylase) the essential amino acid phenylalanine. Half of the phenylalanine required goes into the production of tyrosine; if the diet is rich in tyrosine itself, the requirements for phenylalanine are reduced by about 50%. Phenylalanine hydroxylase is a mixed-function oxygenase: one atom of oxygen is incorporated into water and the other into the hydroxyl of tyrosine. The reductant is the tetrahydrofolate-related cofactor tetrahydrobiopterin, which is maintained in the reduced state by the NADH-dependent enzyme dihydropteridine reductase (DHPR). The catabolism of tyrosine starts with an α-ketoglutarate dependent transamination through the tyrosine transaminase, which generates p-hydroxyphenylpyruvate. The next oxidation step is catalyzed by p-hydroxylphenylpyruvate-dioxygenase and generates homogentisate (2,5-dihydroxyphenyl-1-acetate). In order to split the aromatic ring of homogentisate, a further dioxygenase, homogentistate-oxygenase is required. Through this reaction, maleylacetoacetate is created. Fumarylacetate is then generated by maleylacetoacetate-cis-trans-isomerase through rotation of the carboxyl group created from the hydroxyl group via oxidation. This cis-trans-isomerase contains glutathione as a coenzyme. Fumarylacetoacetate is finally split into acetoactate and fumarate via fumarylacetoacetate-hydrolase through the addition of a water molecule.
Thereby fumarate (also a metabolite of the citric acid cycle) and acetoacetate (3-ketobutyroate) are liberated. Acetoacetate is a ketone body, which is activated with succinyl-CoA, and thereafter it can be converted into acetyl-CoA which in turn can be oxidized by the citric acid cycle or be used for fatty acid synthesis.

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  1. Lehninger, A.L. (2005) Lehninger principles of biochemistry (4 th ed.). New York: W.H Freeman.
  2. Salway, J.G. (2004) Metabolism at a glance (3 rd ed.). Alden, Mass. : Blackwell Pub.